Colony stimulating factor 2 receptor alpha (CSF2RA)

Colony stimulating factor 2 receptor alpha (CSF2RA), also known as CD116, is the ligand-specific alpha subunit of the heterodimeric receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) (UniProt: P15509). It binds GM-CSF with low affinity but associates with the common beta subunit (CSF2RB) to form a high-affinity signaling complex that activates the JAK2-STAT5, MAPK, and PI3K pathways (PubMed: 25762578). Predominantly expressed on myeloid lineage cells, CSF2RA plays a critical role in the production, differentiation, and functional activation of macrophages and granulocytes (NCBI Gene: 1438). Genetic mutations in CSF2RA are linked to hereditary pulmonary alveolar proteinosis (PAP), where impaired surfactant clearance by alveolar macrophages leads to respiratory failure (PubMed: 24335101). In drug development, CSF2RA is targeted by the monoclonal antibody mavrilimumab to inhibit GM-CSF-mediated inflammation in conditions like rheumatoid arthritis and giant cell arteritis (DrugBank: DB12001). Additionally, recombinant GM-CSF therapies like sargramostim utilize this receptor to treat neutropenia and stimulate immune recovery following bone marrow transplantation (PubMed: 10433364). The receptor is also being investigated as a potential target in certain myeloid leukemias where it may be overexpressed or contribute to leukemic cell survival (PubMed: 28246197). Monitoring CSF2RA expression and the presence of anti-GM-CSF autoantibodies is essential for diagnosing and managing surfactant-related lung diseases (PubMed: 21636552).

Other names

GM-CSF receptor alphaCD116Granulocyte-macrophage colony-stimulating factor receptor subunit alphaCSF2RGMR-alphaSMDP4

Mavrilimumab acts as a monoclonal antibody antagonist that binds to the CSF2RA subunit, thereby blocking the binding of GM-CSF and inhibiting downstream pro-inflammatory signaling (DrugBank: DB12001). Conversely, sargramostim and molgramostim are recombinant GM-CSF agonists that bind to the receptor complex to stimulate the production, differentiation, and activation of myeloid cells such as neutrophils and macrophages (PubMed: 10433364).